Fear of crime significantly reduces people's time–space access to and use of public space, notably in high-crime neighborhoods where concerns around personal safety are more acute. One widely used strategy to reduce fear of crime is the regeneration of the built environment. However, tension remains on whether this strategy is effective, and if it is, then where, which and for whom public space interventions work. This research, incorporating a gender perspective, assesses whether neighborhood-level regeneration of public space significantly enhances or reduces residents’ perceptions of safety in deprived urban areas with a gender perspective. To test these impacts, we run a randomized control trial with 100 residents in a high-crime neighborhood in Santiago de Chile. A series of geotagged photographs of the area and ten treatment photo simulations of proposed interventions were rated by residents according to their perceived safety related to crime. The results suggest that: highly unsafe perceptions cluster in specific neighborhood locations and are particularly acute for women; the regeneration of public spaces significantly increases perceived safety for both men and women; and the effectiveness of different interventions is gender-specific. The results suggest, while an effective technique, public space regeneration in deprived neighborhoods can be further optimized through urban design and planning policy that are space- and gender-specific. The technique presented could support researchers and practitioners to understand the spatial distribution of perceptions of safety, to select effective interventions to make deprived neighborhoods feel safer, and to assess the impact of regeneration strategies.